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Tetrahydrofolate and 5‐methyltetrahydrofolate are folates with high antioxidant activity. Identification of the antioxidant pharmacophore
Author(s) -
Rezk Bashir M,
Haenen Guido R.M.M,
van der Vijgh Wim J.F,
Bast Aalt
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01358-9
Subject(s) - antioxidant , chemistry , peroxynitrite , lipid peroxidation , pharmacophore , biochemistry , pterin , pharmacology , superoxide , enzyme , medicine , cofactor
The presumed protective effect of folic acid on the pathogenesis of cardiovascular, hematological and neurological diseases and cancer has been associated with the antioxidant activity of folic acid. Peroxynitrite (PON) scavenging activity and inhibition of lipid peroxidation (LPO) of the physiological forms of folate and of structurally related compounds were tested. It was found that the fully reduced forms of folate, i.e. tetrahydrofolate (THF) and 5‐methyltetrahydrofolate (5‐MTHF), had the most prominent antioxidant activity. It appeared that their protection against LPO is less pronounced than their PON scavenging activity. The antioxidant activity of these forms of folic acid resides in the pterin core, the antioxidant pharmacophore is 4‐hydroxy‐2,5,6‐triaminopyrimidine. It is suggested that an electron donating effect of the 5‐amino group is of major importance for the antioxidant activity of 4‐hydroxy‐2,5,6‐triaminopyrimidine. A similar electron donating effect is probably important for the antioxidant activity of THF and 5‐MTHF.